title: Lipoteichoic acid-deficient Lactobacillus acidophilus regulates downstream signals.
abstract: The trillions of microbes residing within the intestine induce critical signals that either regulate or stimulate host immunity via their bacterial products. To better understand the immune regulation elicited by lipoteichoic acid (LTA)-deficient Lactobacillus acidophilus NCFM in steady state and induced inflammation, we deleted phosphoglycerol transferase gene, which synthesizes LTA in L. acidophilus NCFM. In vitro and in vivo experiments were conducted in order to compare the immune regulatory properties of the L. acidophilus strain deficient in LTA (NCK2025) with its wild-type parent (NCK56) in C57BL/6, C57BL/6 recombination-activation gene 1-deficient (Rag1 (-/-)) and C57BL/6 Rag1(-/-)IL-10(-/-) mice. We demonstrate that NCK2025 significantly activates the phosphorylation of Erk1/2 but downregulates the phosphorylation of Akt1, cytosolic group IV PLA2 and p38 in mouse dendritic cells. Similarly, mice treated orally with NCK2025 exhibit decreased phosphorylation of inflammatory signals (Akt1, cytosolic group IV PLA2 or P38) but upregulate Erk1/2-phosphorylation in colonic epithelial cells in comparison with mice treated with NCK56. In addition, regulation of pathogenic CD4+ T cell induced colitis by NCK2025 was observed in Rag1 (-/-) but not Rag1(-/-)IL-10 (-/-) mice suggests a critical role of IL-10 that may be tightly regulated by Erk1/2 signaling. These data highlight the immunosuppressive properties of NCK2025 to deliver regulatory signals in innate cells, which results in the mitigation of T-cell-induced colitis in vivo.
authors.affiliation: Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Saber
authors.forename: Mojgan
authors.initials: M
authors.lastname: Zadeh
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Pakanati
authors.forename: Praveen
authors.initials: P
authors.lastname: Bere
authors.forename: Todd
authors.initials: T
authors.lastname: Klaenhammer
authors.forename: Mansour
authors.initials: M
authors.lastname: Mohamadzadeh
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007779:Lactobacillus acidophilus / Q000276:immunology / Q000472:pathogenicity; D008070:Lipopolysaccharides / Q000172:deficiency / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000172:deficiency*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D013682:Teichoic Acids; D016753:Interleukin-10; C009900:lipoteichoic acid; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D017855:Transferases (Other Substituted Phosphate Groups); C037247:phosphatidylglycerol - membrane-oligosaccharide glycerophosphotransferase; D054513:Group IV Phospholipases A2